Antihypertensive treatment for kidney transplant recipients.

BACKGROUND: The comparative effects of specific blood pressure (BP) lowering treatments on patient-important outcomes following kidney transplantation are uncertain. Our 2009 Cochrane review found that calcium channel blockers (CCBs) improved graft function and prevented graft loss, while the evidence for other BP-lowering treatments was limited. This is an update of the 2009 Cochrane review. OBJECTIVES: To compare the benefits and harms of different classes and combinations of antihypertensive drugs in kidney transplant recipients. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 3 July 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating any BP-lowering agent in recipients of a functioning kidney transplant for at least two weeks were eligible. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risks of bias and extracted data. Treatment estimates were summarised using the random-effects model and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) processes. The primary outcomes included all-cause death, graft loss, and kidney function. MAIN RESULTS: Ninety-seven studies (8706 participants) were included. One study evaluated treatment in children. The overall risk of bias was unclear to high across all domains. Compared to placebo or standard care alone, CCBs probably reduce all-cause death (23 studies, 3327 participants: RR 0.83, 95% CI 0.72 to 0.95; I2 = 0%; moderate certainty evidence) and graft loss (24 studies, 3577 participants: RR 0.84, 95% CI 0.75 to 0.95; I2 = 0%; moderate certainty evidence). CCBs may make little or no difference to estimated glomerular filtration rate (eGFR) (11 studies, 2250 participants: MD 1.89 mL/min/1.73 m2, 95% CI -0.70 to 4.48; I2 = 48%; low certainty evidence) and acute rejection (13 studies, 906 participants: RR 10.8, 95% CI 0.85 to 1.35; I2 = 0%; moderate certainty evidence). CCBs may reduce systolic BP (SBP) (3 studies, 329 participants: MD -5.83 mm Hg, 95% CI -10.24 to -1.42; I2 = 13%; low certainty evidence) and diastolic BP (DBP) (3 studies, 329 participants: MD -3.98 mm Hg, 95% CI -5.98 to -1.99; I2 = 0%; low certainty evidence). CCBs have uncertain effects on proteinuria. Compared to placebo or standard care alone, angiotensin-converting-enzyme inhibitors (ACEi) may make little or no difference to all-cause death (7 studies, 702 participants: RR 1.13, 95% CI 0.58 to 2.21; I2 = 0%; low certainty evidence), graft loss (6 studies, 718 participants: RR 0.75, 95% CI 0.49 to 1.13; I2 = 0%; low certainty evidence), eGFR (4 studies, 509 participants: MD -2.46 mL/min/1.73 m2, 95% CI -7.66 to 2.73; I2 = 64%; low certainty evidence) and acute rejection (4 studies, 388 participants: RR 1.75, 95% CI 0.76 to 4.04; I2 = 0%; low certainty evidence). ACEi may reduce proteinuria (5 studies, 441 participants: MD -0.33 g/24 hours, 95% CI -0.64 to -0.01; I2 = 67%; low certainty evidence) but had uncertain effects on SBP and DBP. Compared to placebo or standard care alone, angiotensin receptor blockers (ARB) may make little or no difference to all-cause death (6 studies, 1041 participants: RR 0.69, 95% CI 0.36 to 1.31; I2 = 0%; low certainty evidence), eGRF (5 studies, 300 participants: MD -1.91 mL/min/1.73 m2, 95% CI -6.20 to 2.38; I2 = 57%; low certainty evidence), and acute rejection (4 studies, 323 participants: RR 1.00, 95% CI 0.44 to 2.29; I2 = 0%; low certainty evidence). ARBs may reduce graft loss (6 studies, 892 participants: RR 0.35, 95% CI 0.15 to 0.84; I2 = 0%; low certainty evidence), SBP (10 studies, 1239 participants: MD -3.73 mm Hg, 95% CI -7.02 to -0.44; I2 = 63%; moderate certainty evidence) and DBP (9 studies, 1086 participants: MD -2.75 mm Hg, 95% CI -4.32 to -1.18; I2 = 47%; moderate certainty evidence), but has uncertain effects on proteinuria. The effects of CCBs, ACEi or ARB compared to placebo or standard care alone on cardiovascular outcomes (including fatal or nonfatal myocardial infarction, fatal or nonfatal stroke) or other adverse events were uncertain. The comparative effects of ACEi plus ARB dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone were rarely evaluated. Head-to-head comparisons of ACEi, ARB or thiazide versus CCB, ACEi versus ARB, CCB or ACEi versus alpha- or beta-blockers, or ACEi plus CCB dual therapy versus ACEi or CCB monotherapy were scarce. No studies reported outcome data for cancer or life participation. AUTHORS' CONCLUSIONS: For kidney transplant recipients, the use of CCB therapy to reduce BP probably reduces death and graft loss compared to placebo or standard care alone, while ARB may reduce graft loss. The effects of ACEi and ARB compared to placebo or standard care on other patient-centred outcomes were uncertain. The effects of dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone and the comparative effects of different treatments were uncertain.

Assessing clinician competence in the delivery of cognitive-behavioural therapy for eating disorders: development of the Cognitive-Behavioural Therapy Scale for Eating Disorders (CBTS-ED).

Evidence-based cognitive-behaviour therapy for eating disorders (CBT-ED) differs from other forms of CBT for psychological disorders, making existing generic CBT measures of therapist competence inadequate for evaluating CBT-ED. This study developed and piloted the reliability of a novel measure of therapist competence in this domain-the Cognitive Behaviour Therapy Scale for Eating Disorders (CBTS-ED). Initially, a team of CBT-ED experts developed a 26-item measure, with general (i.e. present in every session) and specific (context- or case-dependent) items. To determine statistical properties of the measure, nine CBT-ED experts and eight non-experts independently observed six role-played mock CBT-ED therapy sessions, rating the therapists' performance using the CBTS-ED. The inter-item consistency (Cronbach's alpha and McDonald's omega) and inter-rater reliability (ICC) were assessed, as appropriate to the clustering of the items. The CBTS-ED demonstrated good internal consistency and moderate/good inter-rater reliability for the general items, at least comparable to existing generic CBT scales in other domains. An updated version is proposed, where five of the 16 "specific" items are reallocated to the general group. These preliminary results suggest that the CBTS-ED can be used effectively across both expert and non-expert raters, though less experienced raters might benefit from additional training in its use.

Epidemiology of cardiovascular death in kidney failure: An Australian and New Zealand cohort study using data linkage.

AIM: Cardiovascular mortality risk evolves over the lifespan of kidney failure (KF), as patients develop comorbid disease and transition between treatment modalities. Absolute cardiovascular death rates would help inform clinical practice and health-care provision, but are not well understood across a continuum of dialysis and transplant states. We aimed to characterize cardiovascular death across the natural history of KF using a lifespan approach. METHODS: We performed a population-based cohort study of incident patients commencing kidney replacement therapy in Australia and New Zealand. Cardiovascular deaths were identified using data linkage to national death registers. We estimated the probability of death and kidney transplant using multi-state models, and calculated rates of graft failure and cardiovascular death across demographic factors and comorbidities. RESULTS: Among 60 823 incident patients followed over 381 874 person-years, 25% (8492) of deaths were from cardiovascular disease. At 15 years from treatment initiation, patients had a 15.2% probability of cardiovascular death without being transplanted, but only 2.3% probability of cardiovascular death post-transplant. Females had a 3% lower probability of cardiovascular death at 15 years (15.3% vs. 18.6%) but 4% higher probability of non-cardiovascular death (54.5% vs. 50.8%). Within the first year of dialysis, cardiovascular mortality peaked in the second month and showed little improvement across treatment era. CONCLUSION: Despite improvements over time, cardiovascular death remains common in KF, particularly among the dialysis population and in the first few months of treatment. Multi-state models can provide absolute measures of cardiovascular mortality across both dialysis and transplant states.

Interventions for atypical haemolytic uraemic syndrome.

BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder characterised by thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. The condition is primarily caused by inherited or acquired dysregulation of complement regulatory proteins with ~40% of those affected aged < 18 years. Historically, kidney failure and death were common outcomes, however, improved understanding of the condition has led to discovery of novel therapies. OBJECTIVES: To evaluate the benefits and harms of interventions for aHUS. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies for randomised controlled studies (RCTs) up to 3 September 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. MEDLINE(OVID) 1946 to 27 July 2020 and EMBASE (OVID) 1974 to 27 July 2020 were searched for non-RCTs. SELECTION CRITERIA: All randomised and non-randomised clinical trials comparing an intervention with placebo, an intervention with supportive therapy, or two or more interventions for aHUS were included. Given the rare nature of the condition in question, prospective single-arm studies of any intervention for aHUS were also included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted pre-specified data from eligible studies and evaluated risk of bias using a newly developed tool based on existing Cochrane criteria. As statistical meta-analysis was not appropriate, qualitative analysis of data was then performed. MAIN RESULTS: We included five single-arm studies, all of which evaluated terminal complement inhibition for the treatment of aHUS. Four studies evaluated the short-acting C5 inhibitor eculizumab and one study evaluated the longer-acting C5 inhibitor ravulizumab. All included studies within the review were of non-randomised, single-arm design. Thus, risk of bias is high, and it is challenging to draw firm conclusions from this low-quality evidence. One hundred patients were included within three primary studies evaluating eculizumab, with further data reported from 37 patients in a secondary study. Fifty-eight patients were included in the ravulizumab study. After 26 weeks of eculizumab therapy there were no deaths and a 70% reduction in the number of patients requiring dialysis. Complete thrombotic microangiopathic (TMA) response was observed in 60% of patients at 26 weeks and 65% at two years. After 26 weeks of ravulizumab therapy four patients had died (7%) and complete TMA response was observed in 54% of patients. Substantial improvements were seen in estimated glomerular filtration rate and health-related quality of life in both eculizumab and ravulizumab studies. Serious adverse events occurred in 42% of patients, and meningococcal infection occurred in two patients, both treated with eculizumab. AUTHORS' CONCLUSIONS: When compared with historical data, terminal complement inhibition appears to offer favourable outcomes in patients with aHUS, based upon very low-quality evidence drawn from five single-arm studies. It is unlikely that an RCT will be conducted in aHUS and therefore careful consideration of future single-arm data as well as longer term follow-up data will be required to better understand treatment duration, adverse outcomes and risk of disease recurrence associated with terminal complement inhibition.

Incidence of Ischaemic Heart Disease in Men and Women With End-Stage Kidney Disease: A Cohort Study.

BACKGROUND: The incidence of ischaemic heart disease (IHD) has fallen consistently in the general population; attributed to effective primary prevention strategies. Differences in incidence have been demonstrated by sex. Whether this fall in incidence and sex differences is mirrored in people with end-stage kidney disease (ESKD) is unclear. We aimed to establish the relative risk of IHD events in the ESKD population. METHODS: We performed a retrospective cohort study from 2000 to 2010 in people with ESKD in New South Wales. We performed data linkage of the Australia and New Zealand Dialysis and Transplant Registry and state wide hospital admission and death registry data and compared this to general population data. The primary outcome was the incidence rate, incidence rate ratio (IRR), and time-trend for any IHD event. We calculated these using indirect standardisation by IHD event. RESULTS: 10,766 participants, contributed 44,149 years of observation time. Incidence rates were substantially higher than the general population for all IHD events (any IHD event: IRR 1.8, 95% confidence interval [CI] 1.7-1.9 for men, IRR 3.4, 95% CI 3.1-3.6 for women). Excess risk was higher in younger people (age 30-49 IRR 4.8, 95% CI 4.2-5.4), and in women with a three-fold increase risk overall and nearly a 10-fold increase in risk in young women (female age 30-49 years: IRR 9.8 95% CI 7.7-12.3), results were similar for angina and acute myocardial infarction. Ischaemic heart disease rates showed some decline for men over time, (ratio of IRR 0.93, 95% CI 0.90-0.95) but were stable for women (ratio of IRR 0.97, 95% CI 0.94-1.01). CONCLUSIONS: People with ESKD have substantially higher rates of IHD than the general population, especially women, in whom no improvement appears evident over the past 10 years.

Death From Stroke in End-Stage Kidney Disease.

Background and Purpose- People with end-stage kidney disease (ESKD) are at greater risk of stroke. We aimed to compare stroke mortality between the ESKD population and the general population. Methods- We included all patients with incident ESKD in Australia, 1980 to 2013, and New Zealand, 1988 to 2012. The primary cause of death was ascertained using data linkage with national death registers. We produced standardized mortality ratios for stroke deaths, by age, sex, and calendar year. Results- We included 60 823 patients with ESKD, where 941 stroke deaths occurred during 381 874 person-years. Patients with ESKD had >3× the stroke deaths compared with the general population (standardized mortality ratio, 3.4; 95% CI, 3.2-3.6), markedly higher in younger people and women. The greatest excess was in intracerebral hemorrhages (standardized mortality ratio, 5.2; 95% CI, 4.5-5.9). Excess stroke deaths in patients with ESKD decreased over time, although were still double in 2013 (2013 standardized mortality ratio, 2.1; 95% CI, 1.5-2.9). Conclusions- People with ESKD experience much greater stroke mortality with the greatest difference for women and younger people. However, mortality has improved over time.

Chronic Kidney Disease.

The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m2, or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR declines. Interventions targeting specific symptoms, or aimed at supporting educational or lifestyle considerations, make a positive difference to people living with CKD. Inequity in access to services for this disease disproportionally affects disadvantaged populations, and health service provision to incentivise early intervention over provision of care only for advanced CKD is still evolving in many countries.

Immunosuppressive treatment for proliferative lupus nephritis.

BACKGROUND: Cyclophosphamide, in combination with corticosteroids, has been first-line treatment for inducing disease remission for proliferative lupus nephritis, reducing death at five years from over 50% in the 1950s and 1960s to less than 10% in recent years. Several treatment strategies designed to improve remission rates and minimise toxicity have become available. Treatments, including mycophenolate mofetil (MMF) and calcineurin inhibitors, alone and in combination, may have equivalent or improved rates of remission, lower toxicity (less alopecia and ovarian failure) and uncertain effects on death, end-stage kidney disease (ESKD) and infection. This is an update of a Cochrane review first published in 2004 and updated in 2012. OBJECTIVES: Our objective was to assess the evidence and evaluate the benefits and harms of different immunosuppressive treatments in people with biopsy-proven lupus nephritis. The following questions relating to management of proliferative lupus nephritis were addressed: 1) Are new immunosuppressive agents superior to or as effective as cyclophosphamide plus corticosteroids? 2) Which agents, dosages, routes of administration and duration of therapy should be used? 3) Which toxicities occur with the different treatment regimens? SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 2 March 2018 with support from the Cochrane Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing any immunosuppressive treatment for biopsy-proven class III, IV, V+III and V+VI lupus nephritis in adult or paediatric patients were included. DATA COLLECTION AND ANALYSIS: Data were abstracted and the risks of bias were assessed independently by two authors. Dichotomous outcomes were calculated as risk ratio (RR) and measures on continuous scales calculated as mean differences (MD) with 95% confidence intervals (CI). The primary outcomes were death (all causes) and complete disease remission for induction therapy and disease relapse for maintenance therapy. Evidence certainty was determined using GRADE. MAIN RESULTS: In this review update, 26 new studies were identified, to include 74 studies involving 5175 participants overall. Twenty-nine studies included children under the age of 18 years with lupus nephritis, however only two studies exclusively examined the treatment of lupus nephritis in patients less than 18 years of age.Induction therapy Sixty-seven studies (4791 participants; median 12 months duration (range 2.5 to 48 months)) reported induction therapy. The effects of all treatment strategies on death (all causes) and ESKD were uncertain (very low certainty evidence) as this outcome occurred very infrequently. Compared with intravenous (IV) cyclophosphamide, MMF may have increased complete disease remission (RR 1.17, 95% CI 0.97 to 1.42; low certainty evidence), although the range of effects includes the possibility of little or no difference.Compared to IV cyclophosphamide, MMF is probably associated with decreased alopecia (RR 0.29, 95% CI 0.19 to 0.46; 170 less (129 less to 194 less) per 1000 people) (moderate certainty evidence), increased diarrhoea (RR 2.42, 95% CI 1.64 to 3.58; 142 more (64 more to 257 more) per 1000 people) (moderate certainty evidence) and may have made little or no difference to major infection (RR 1.02, 95% CI 0.67 to 1.54; 2 less (38 less to 62 more) per 1000 people) (low certainty evidence). It is uncertain if MMF decreased ovarian failure compared to IV cyclophosphamide because the certainty of the evidence was very low (RR 0.36, 95% CI 0.06 to 2.18; 26 less (39 less to 49 more) per 1000 people). Studies were not generally designed to measure ESKD.MMF combined with tacrolimus may have increased complete disease remission (RR 2.38, 95% CI 1.07 to 5.30; 336 more (17 to 1048 more) per 1000 people (low certainty evidence) compared with IV cyclophosphamide, however the effects on alopecia, diarrhoea, ovarian failure, and major infection remain uncertain. Compared to standard of care, the effects of biologics on most outcomes were uncertain because of low to very low certainty of evidence.Maintenance therapyNine studies (767 participants; median 30 months duration (range 6 to 63 months)) reported maintenance therapy. In maintenance therapy, disease relapse is probably increased with azathioprine compared with MMF (RR 1.75, 95% CI 1.20 to 2.55; 114 more (30 to 236 more) per 1000 people (moderate certainty evidence). Multiple other interventions were compared as maintenance therapy, but patient-outcome data were sparse leading to imprecise estimates. AUTHORS' CONCLUSIONS: In this review update, studies assessing treatment for proliferative lupus nephritis were not designed to assess death (all causes) or ESKD. MMF may lead to increased complete disease remission compared with IV cyclophosphamide, with an acceptable adverse event profile, although evidence certainty was low and included the possibility of no difference. Calcineurin combined with lower dose MMF may improve induction of disease remission compared with IV cyclophosphamide, but the comparative safety profile of these therapies is uncertain. Azathioprine may increase disease relapse as maintenance therapy compared with MMF.

Le trouble de l'accès hyperphagique: Aperçu actualisé à l'intention des professionnels des soins primaires.

OBJECTIF: Fournir aux professionnels des soins primaires un aperçu actualisé du trouble de l'accès hyperphagique (TAH), qui comporte des recommandations pertinentes. QUALITÉ DES DONNÉES: Une recension a été effectuée dans PubMed, PsycInfo et Google Scholar, sans restrictions temporelles, à l'aide des expressions clés en anglais binge eating disorder, treatment, review, guidelines, psychotherapy, primary care et pharmacotherapy. Le niveau des données probantes pour toutes les recommandations varie de I à III. MESSAGE PRINCIPAL: Le trouble de l'accès hyperphagique est associé à une grande détresse et à une incapacité considérable chez le patient, ainsi qu'à des comorbidités médicales et psychiatriques; il a été ajouté dans la 5e édition du Manuel diagnostique et statistique des troubles mentaux, en 2013. Les médecins de soins primaires sont bien placés pour le dépistage, le diagnostic et l'amorce du traitement du TAH. Une approche par étapes du traitement commence par un développement personnel guidé, suivi par l'ajout ou le changement de la pharmacothérapie, ou par une psychothérapie individuelle, au besoin. Les psychothérapies dont l'efficacité est le plus corroborée par la recherche sont la thérapie cognitivo-comportementale, la thérapie interpersonnelle et la thérapie comportementale dialectique. CONCLUSION: Cet aperçu présente des conseils sur le dépistage, le diagnostic et les approches thérapeutiques fondés sur les données probantes actuellement disponibles, de même les avis d'un groupe diversifié d'experts, pour aider à orienter les cliniciens lorsque les données probantes sont limitées.

Cognition in chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Cognitive impairment is common in people with chronic kidney disease (CKD) and associated with increased morbidity and mortality. Subtle changes can impact engagement with healthcare, comprehension, decision-making, and medication adherence. We aimed to systematically summarise evidence of cognitive changes in CKD. METHODS: We searched MEDLINE (March 2016) for cross-sectional, cohort or randomised studies that measured cognitive function in people with CKD (PROSPERO, registration number CRD42014015226). The CKD population included people with eGFR < 60 mL/min/1.73 m2, not receiving renal replacement therapy, in any research setting. We conducted a meta-analysis using random effects, expressed as standardised mean differences (SMD) with 95% confidence intervals (CI). Outcomes were performance in eight cognitive domains. Bias was assessed with the Newcastle-Ottawa Scale (NOS). RESULTS: We identified 44 studies reporting sufficient data for synthesis (51,575 participants). Mean NOS score for cohort studies was 5.8/9 and for cross-sectional 5.4/10. Studies were deficient in NOS outcome and selection due to poor methods reporting and in comparison group validity of demographics and chronic disease status. CKD patients (eGFR < 60 mL/min/1.73 m2) performed worse than control groups (eGFR ≥ 60 mL/min/1.73 m2) on Orientation & Attention (SMD -0.79, 95% CI, -1.44 to -0.13), Language (SMD -0.63, 95% CI, -0.85 to -0.41), Concept Formation & Reasoning (SMD -0.63, 95% CI, -1.07 to -0.18), Executive Function (SMD -0.53, 95% CI, -0.85 to -0.21), Memory (SMD -0.48, 95% CI, -0.79 to -0.18), and Global Cognition (SMD -0.48, 95% CI, -0.72 to -0.24). Construction & Motor Praxis and Perception were unaffected (SMD -0.29, 95% CI, -0.90 to 0.32; SMD -1.12, 95% CI, -4.35 to 2.12). Language scores dropped with eGFR (<45 mL/min/1.73 m2 SMD -0.86, 95% CI, -1.25 to -46; 30 mL/min/1.73 m2 SMD -1.56, 95% CI, -2.27 to -0.84). Differences in Orientation & Attention were greatest at eGFR < 45 mL/min/1.73 m2 (SMD -4.62, 95% CI, -4.68 to -4.55). Concept Formation & Reasoning differences were greatest at eGFR < 45 mL/min/1.73 m2 (SMD -4.27, 95% CI, -4.23 to -4.27). Differences in Executive Functions were greatest at eGFR < 30 mL/min/1.73 m2 (SMD -0.54, 95% CI, -1.00 to -0.08). CONCLUSIONS: Cognitive changes occur early in CKD, and skills decline at different rates. Orientation & Attention and Language are particularly affected. The cognitive impact of CKD is likely to diminish patients' capacity to engage with healthcare decisions. An individual's cognitive trajectory may deviate from average.

Cognition in People With End-Stage Kidney Disease Treated With Hemodialysis: A Systematic Review and Meta-analysis.

BACKGROUND: Cognitive impairment is associated with poorer quality of life, risk for hospitalization, and mortality. Cognitive impairment is common in people with end-stage kidney disease treated with hemodialysis, yet the severity and specific cognitive deficits are uncertain. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Adults receiving hemodialysis compared with the general population, people with non-dialysis-dependent chronic kidney disease (NDD-CKD), people receiving peritoneal dialysis, or people with nondialyzed chronic kidney failure. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials, cohort or cross-sectional studies without language restriction. INDEX TESTS: Validated neuropsychological tests of cognition. OUTCOMES: Cognitive test scores, aggregated by cognitive domain: orientation and attention, perception, memory, language, construction and motor performance, concept formation and reasoning, and executive functions. RESULTS: 42 studies of 3,522 participants. Studies were of high or uncertain risk of bias, assessed by the Newcastle-Ottawa Scale. People treated with hemodialysis had worse cognition than the general population, particularly in attention (n=22; standardized mean difference [SMD], -0.93; 95% CI, -1.18 to -0.68). Hemodialysis patients performed better than nondialyzed patients with chronic kidney failure in attention (n=6; SMD, 0.70; 95% CI, 0.45 to 0.96) and memory (n=6; SMD, 0.36; 95% CI, 0.08 to 0.63), but had poorer memory than the general population (n=16; SMD, -0.41; 95% CI, -0.91 to 0.09) and people with NDD-CKD (n=5; SMD, -0.40; 95% CI, -0.60 to -0.21). There were insufficient data to show other differences among people receiving hemodialysis and those receiving peritoneal dialysis or with NDD-CKD. LIMITATIONS: Potentially biased studies, not wholly adjusted for education. High heterogeneity, mainly due to the large variety of tests used to assess cognition. CONCLUSIONS: People treated with hemodialysis have impaired cognitive function compared to the general population, particularly in the domains of orientation and attention and executive function. Cognitive deficits in specific domains should be further explored in this population and should be considered when approaching education and chronic disease management.

Risk Factors for Stroke in People with End-Stage Kidney Disease: A Cohort Study.

BACKGROUND: It is unclear how traditional cardiovascular risk factors and different treatment modalities for end-stage kidney disease (ESKD) affect stroke risk in people with ESKD. We aimed to identify the risk factors for stroke (ischemic and hemorrhagic) in people with ESKD. METHODS: We conducted a retrospective cohort study using data linkage between the Australian and New Zealand Dialysis and Transplant Registry, clinical and administrative datasets. Using Cox proportional hazards models, we estimated the magnitudes of risk of hospitalization with different subtypes of strokes associated with traditional cardiovascular risk factors and ESKD treatment modalities (hemodialysis (HD), peritoneal dialysis (PD) and kidney transplantation). Results were expressed as hazard ratios (HRs) with 95% CIs. RESULTS: A total of 10,745 people received treatment for ESKD in New South Wales, Australia, between 2000 and 2010. We observed 640 hospitalizations for stroke in 49,497 person-years of follow-up (129.4 per 10,000 person years). Some risk factors were consistent with those found in the general population, including smoking and a history of previous stroke. Other risk factors were novel for people with ESKD. Women were 85% more likely to have an intracerebral hemorrhage (HR 1.85, 95% CI 1.22-2.79) and 30% more likely to have an ischemic stroke (HR 1.30, 95% CI 1.01-1.66) than men. Compared to people on HD, people with kidney transplants had a 65% lower risk of intracerebral hemorrhage (HR 0.35, 95% CI 0.18-0.69) but a similar risk of ischemic stroke (HR 0.97, 95% CI 0.64-1.49). People on PD had a 36% higher risk of ischemic stroke (HR 1.36, 95% CI 1.05-1.76) but a similar risk of intracerebral hemorrhage compared to people on HD (HR 0.69, 95% CI 0.43-1.11). CONCLUSIONS: These findings could be used to establish reliable estimates of the risk of stroke in people with ESKD and identify those who are most likely to benefit from preventive treatments.

Early Precut Sphincterotomy Does Not Increase Risk During Endoscopic Retrograde Cholangiopancreatography in Patients With Difficult Biliary Access: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND & AIMS: Use of precut sphincterotomy during endoscopic retrograde cholangiopancreatography (ERCP) can increase the odds for cannulation success but is associated with increased risk of post-ERCP pancreatitis. Earlier, rather than delayed, use of precut sphincterotomy for cases with difficult biliary access might reduce this risk. We performed a meta-analysis of randomized controlled trials to determine how early use of precut sphincterotomy affects the risk of pancreatitis and rate of cannulation success compared with persistent standard cannulation. METHODS: We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials, along with meeting abstracts, through August 2014 for randomized controlled trials in which early precut sphincterotomy was compared with persistent standard cannulation in adults with difficult biliary access. Outcomes considered included primary cannulation success, overall cannulation success, incidence of post-ERCP pancreatitis, and overall adverse event rate. Findings from a random-effects model were expressed as pooled risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: We analyzed data from 5 studies (523 participants). The incidence of post-ERCP pancreatitis and success of overall cannulation did not differ significantly between the early precut and persistent standard therapy groups. Early use of precut sphincterotomy was associated with increased odds for primary cannulation success (RR, 1.32; 95% CI, 1.04-1.68). In subgroup analysis of studies that involved only fully qualified biliary endoscopists (not fellows), we found a significant reduction in risk of pancreatitis among patients receiving early precut vs the standard technique (RR, 0.29; 95% CI, 0.10-0.86). CONCLUSION: Compared with standard therapy, early use of precut sphincterotomy did not increase the risk of post-ERCP pancreatitis in a meta-analysis. When the procedure is performed by qualified biliary endoscopists, early precut can reduce the risk of post-ERCP pancreatitis. Rates of primary cannulation increase with early precut. Further studies are needed to confirm these findings.

Chronic kidney disease and the risk of stroke: a systematic review and meta-analysis.

BACKGROUND: People with chronic kidney disease (CKD) have an increased risk of stroke but the magnitude of increased risk and the independent effects of glomerular filtration rate (GFR) and albuminuria are unclear. We aimed to quantify the association between the independent and combined effects of GFR and albuminuria on stroke risk. METHODS: We searched MEDLINE and EMBASE (February 2014) for cohort studies or randomized controlled trials (RCTs) which reported stroke incidence in adults with a baseline measurement of GFR and/or albuminuria. We extracted study and participant characteristics, risk of bias and relative risks (RR, with confidence interval; CI) of stroke associated with GFR and/or quantity of albuminuria, synthesized data using random effects meta-analysis and explored heterogeneity using meta-regression. RESULTS: We identified 83 studies; 63 cohort studies (2 085 225 participants) and 20 RCTs (168 516 participants) reporting 30 392 strokes. There was an inverse linear relationship between GFR and risk of stroke, with risk of stroke increasing 7% (RR: 1.07, CI: 1.04-1.09) for every 10 mL/min/1.73 m(2) decrease in GFR. A 25 mg/mmol increase in albumin-creatinine ratio was associated with a 10% increased risk of stroke (RR: 1.10, 95% CI: 1.01-1.20). The effect of albuminuria was independent of GFR. Results were not different across subtypes of stroke, sex and varying prevalence of cardiovascular risk factors. CONCLUSIONS: Stroke risk increases linearly and additively with declining GFR and increasing albuminuria. CKD staging may also be a useful clinical tool for identifying people who may benefit most from interventions to reduce cardiovascular risk.

Pulmonary Vein Isolation Compared to Rate Control in Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

BACKGROUND: Atrial fibrillation (AF) often coexists with congestive cardiac failure (CCF), with multiple treatment options available. METHODS: Systematic review and meta-analysis of randomised control trials (RCT) comparing pulmonary vein isolation (PVI), pharmacological rate control, and atrioventricular junction ablation with pacemaker insertion (AVJAP) for AF, with a subgroup analysis in patients with CCF. We analysed changes in left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, six-minute walk distance (6MWD), treadmill exercise time, and treatment complications. Results were expressed as weighted mean differences (WMD) with 95% Confidence-Intervals (95%CI). RESULTS: We included seven RCT (425 participants). PVI was associated with a greater increase in LVEF (WMD+6.5%, 95%CI:+0.6to+12.5) and decrease in MLHFQ score (WMD-11.0, 95%CI:-2.6to-19.4) than pharmacological rate control in patients with CCF. PVI was also associated with a greater increase in LVEF (WMD+9.0%, 95%CI:+6.3to+11.7) and 6MWD (WMD+55.0metres, 95%CI:+34.9to+75.1), and decrease in MLHFQ score (WMD-22.0, 95%CI:-17.0to-27.0), compared to AVJAP in patients with CCF. Irrespective of cardiac function, pharmacological rate control had similar effects to AVJAP on LVEF (WMD+0.6%, 95%CI:-8.3to+9.4) and treadmill exercise time (WMD+0.5minutes, 95%CI:-0.4to+1.3). CONCLUSIONS: Our results support the clinical implementation of PVI over AVJAP or pharmacological rate control in AF patients with CCF, who may or may not have already trialled pharmacological rhythm control.

Belatacept for kidney transplant recipients.

BACKGROUND: Most people who receive a kidney transplant die from either cardiovascular disease or cancer before their transplant fails. The most common reason for someone with a kidney transplant to lose the function of their transplanted kidney necessitating return to dialysis is chronic kidney transplant scarring. Immunosuppressant drugs have side effects that increase risks of cardiovascular disease, cancer and chronic kidney transplant scarring. Belatacept may provide sufficient immunosuppression while avoiding unwanted side effects of other immunosuppressant drugs. However, high rates of post-transplant lymphoproliferative disease (PTLD) have been reported when belatacept is used in particular kidney transplant recipients at high dosage. OBJECTIVES: 1) Compare the relative efficacy of belatacept versus any other primary immunosuppression regimen for preventing acute rejection, maintaining kidney transplant function, and preventing death. 2) Compare the incidence of several adverse events: PTLD; other malignancies; chronic transplant kidney scarring (IF/TA); infections; change in blood pressure, lipid and blood sugar control. 3) Assess any variation in effects by study, intervention and recipient characteristics, including: differences in pre-transplant Epstein Barr virus serostatus; belatacept dosage; and donor-category (living, standard criteria deceased, or extended criteria deceased). SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 1 September 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: Randomised controlled trials (RCT) that compared belatacept versus any other immunosuppression regimen in kidney transplant recipients were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data for study quality and transplant outcomes and synthesized results using random effects meta-analysis, expressed as risk ratios (RR) and mean differences (MD), both with 95% confidence intervals (CI).  Subgroup analyses and univariate meta-regression were used to investigate potential heterogeneity. MAIN RESULTS: We included five studies that compared belatacept and calcineurin inhibitors (CNI) that reported data from a total of 1535 kidney transplant recipients. Of the five studies, three (478 participants) compared belatacept and cyclosporin and two (43 recipients) compared belatacept and tacrolimus. Co-interventions included basiliximab (4 studies, 1434 recipients); anti-thymocyte globulin (1 study, 89 recipients); alemtuzumab (1 study, 12 recipients); mycophenolate mofetil (MMF, 5 studies, 1509 recipients); sirolimus (1 study, 26 recipients) and prednisone (5 studies, 1535 recipients).Up to three years following transplant, belatacept and CNI-treated recipients were at similar risk of dying (4 studies, 1516 recipients: RR 0.75, 95% CI 0.39 to 1.44), losing their kidney transplant and returning to dialysis (4 studies, 1516 recipients: RR 0.91, 95% CI 0.61 to 1.38), and having an episode of acute rejection (4 studies, 1516 recipients: RR 1.56, 95% CI 0.85 to 2.86). Belatacept-treated kidney transplant recipients were 28% less likely to have chronic kidney scarring (3 studies, 1360 recipients: RR 0.72, 95% CI 0.55 to 0.94) and also had better graft function (measured glomerular filtration rate (GFR) (3 studies 1083 recipients): 10.89 mL/min/1.73 m², 95% CI 4.01 to 17.77; estimated GFR (4 studies, 1083 recipients): MD 9.96 mL/min/1.73 m², 95% CI 3.28 to 16.64) than CNI-treated recipients. Blood pressure was lower (systolic (2 studies, 658 recipients): MD -7.51 mm Hg, 95% CI -10.57 to -4.46; diastolic (2 studies, 658 recipients): MD -3.07 mm Hg, 95% CI -4.83 to -1.31, lipid profile was better (non-HDL (3 studies 1101 recipients): MD -12.25 mg/dL, 95% CI -17.93 to -6.57; triglycerides (3 studies 1101 recipients): MD -24.09 mg/dL, 95% CI -44.55 to -3.64), and incidence of new-onset diabetes after transplant was reduced by 39% (4 studies (1049 recipients): RR 0.61, 95% CI 0.40 to 0.93) among belatacept-treated versus CNI-treated recipients.Risk of PTLD was similar in belatacept and CNI-treated recipients (4 studies, 1516 recipients: RR 2.79, 95% CI 0.61 to 12.66) and was no different among recipients who received different belatacept dosages (high versus low dosage: ratio of risk ratios (RRR) 1.06, 95% CI 0.11 to 9.80, test of difference = 0.96) or among those who were Epstein Barr virus seronegative compared with those who were seropositive before their kidney transplant (seronegative versus seropositive; RRR 1.49, 95% CI 0.15 to 14.76, test for difference = 0.73).The belatacept dose used (high versus low), type of donor kidney the recipient received (extended versus standard criteria) and whether the kidney transplant recipient received tacrolimus or cyclosporin made no difference to kidney transplant survival, incidence of acute rejection or estimated GFR. Selective outcome reporting meant that data for some key subgroup comparisons were sparse and that estimates of the effect of treatment in these groups of recipients remain imprecise. AUTHORS' CONCLUSIONS: There is no evidence of any difference in the effectiveness of belatacept and CNI in preventing acute rejection, graft loss and death, but treatment with belatacept is associated with less chronic kidney scarring and better kidney transplant function. Treatment with belatacept is also associated with better blood pressure and lipid profile and a lower incidence of diabetes versus treatment with a CNI. Important side effects (particularly PTLD) remain poorly reported and so the relative benefits and harms of using belatacept remain unclear. Whether short-term advantages of treatment with belatacept are maintained over the medium- to long-term or translate into better cardiovascular outcomes or longer kidney transplant survival with function remains unclear. Longer-term, fully reported and published studies comparing belatacept versus tacrolimus are needed to help clinicians decide which patients might benefit most from using belatacept.

Induction and maintenance treatment of proliferative lupus nephritis: a meta-analysis of randomized controlled trials.

BACKGROUND: Lupus nephritis accounts for ~1% of patients starting dialysis therapy. Treatment regimens combining cyclophosphamide with steroids preserve kidney function but have significant side effects. Newer immunosuppressive agents may have improved toxicity profiles. STUDY DESIGN: Systematic review and random-effects meta-analysis, searching MEDLINE (1966 to April 2012), EMBASE (1988-2011), and the Cochrane Renal Group Specialised Register. SETTING & POPULATION: Patients with biopsy-proven proliferative lupus nephritis (classes III, IV, V+III, and V+IV). SELECTION CRITERIA: Randomized controlled trials. INTERVENTION: Immunosuppressive treatment regimens used for induction and maintenance therapy of lupus nephritis. OUTCOMES: Mortality, renal remission and relapse, doubling of creatinine level, proteinuria, incidence of end-stage kidney disease, ovarian failure, alopecia, leukopenia, infections, diarrhea, vomiting, malignancy, and bladder toxicity. RESULTS: 45 trials (2,559 participants) of induction therapy and 6 (514 participants) of maintenance therapy were included. In induction regimens comparing mycophenolate mofetil (MMF) with intravenous cyclophosphamide, there was no significant difference in mortality (7 studies, 710 patients; risk ratio [RR], 1.02; 95% CI, 0.52-1.98), incidence of end-stage kidney disease (3 studies, 231 patients; RR, 0.71; 95% CI, 0.27-1.84), complete renal remission (6 studies, 686 patients; RR, 1.39; 95% CI, 0.99-1.95), and renal relapse (1 study, 140 patients; RR, 0.97; 95% CI, 0.39-2.44). MMF-treated patients had significantly lower risks of ovarian failure (2 studies, 498 patients; RR, 0.15; 95% CI, 0.03-0.80) and alopecia (2 studies, 522 patients; RR, 0.22; 95% CI, 0.06-0.86). In maintenance therapy comparing azathioprine with MMF, the risk of renal relapse was significantly higher (3 studies, 371 patients; RR, 1.83; 95% CI, 1.24-2.71). LIMITATIONS: Heterogeneity in interventions and definitions of remission and lack of long-term outcome reporting. CONCLUSIONS: MMF is as effective as cyclophosphamide in achieving remission in lupus nephritis, but is safer, with a lower risk of ovarian failure. MMF is more effective than azathioprine in maintenance therapy for preventing relapse, with no difference in clinically important side effects.

Functions of disordered eating behaviors: a qualitative analysis of the lived experience and clinician perspectives.

BACKGROUND: One method to improve treatment outcomes for individuals with eating disorders (EDs) may be understanding and targeting individuals' motives for engaging in DE behaviors-or the functions of DE behaviors. The goal of this study was to investigate and categorize the various functions of DE behaviors from the perspectives of adults who engage in DE behaviors and clinicians who treat EDs. METHODS: Individuals who engage in DE behaviors (n = 16) and clinicians who treat EDs (n = 14) were interviewed, and a thematic analysis was conducted to determine key functions of DE behaviors. RESULTS: Four main functions of DE behaviors were identified by the authors: (1) alleviating shape, weight, and eating concerns; (2) regulating emotions; (3) regulating one's self-concept; and (4) regulating interpersonal relationships/communicating with others. CONCLUSIONS: Differences in participant responses, particularly regarding the relevance of alleviating shape and weight concerns as an DE behavior function, highlight the importance of individualized conceptualizations of DE behavior functions for any given client.

There are many reasons why individuals engage in disordered eating (DE) behaviors, and gathering information on these functions of one's DE behaviors might help clinicians decide which treatments to administer to individual clients. This study identified and organized numerous functions of DE behaviors based on perspectives of both adults who engage in DE behaviors and clinicians who treat EDs. These functions can be largely grouped into four categories: (1) reducing concerns about one's shape, weight, and/or eating habits; (2) managing one's emotions; (3) managing one's beliefs about themselves as a person; and (4) managing relationships with others or communicating with others. Using treatments that address these reasons for one's DE behaviors may be beneficial for clients.

Treatment for lupus nephritis.

BACKGROUND: Cyclophosphamide, in combination with corticosteroids has been used to induce remission in proliferative lupus nephritis, the most common kidney manifestation of the multisystem disease, systemic lupus erythematosus. Cyclophosphamide therapy has reduced mortality from over 70% in the 1950s and 1960s to less than 10% in recent years. Cyclophosphamide combined with corticosteroids preserves kidney function but is only partially effective and may cause ovarian failure, infection and bladder toxicity. Several new agents, including mycophenolate mofetil (MMF), suggest reduced toxicity with equivalent rates of remission. This is an update of a Cochrane review first published in 2004. OBJECTIVES: To assess the benefits and harms of different immunosuppressive treatments in biopsy-proven proliferative lupus nephritis. SEARCH METHODS: For this update, we searched the Cochrane Renal Group's Specialised Register (up to 15 April 2012) through contact with the Trials' Search Coordinator using search terms relevant to this review. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing any treatments for biopsy-proven lupus nephritis in both adult and paediatric patients with class III, IV, V +III and V +IV lupus nephritis were included. All immunosuppressive treatments were considered. DATA COLLECTION AND ANALYSIS: Data were abstracted and quality assessed independently by two authors, with differences resolved by discussion. Dichotomous outcomes were reported as risk ratio (RR) and measurements on continuous scales reported as mean differences (MD) with 95% confidence intervals (CI). MAIN RESULTS: We identified 50 RCTs involving 2846 participants. Of these, 45 studies (2559 participants) investigated induction therapy, and six studies (514 participants), considered maintenance therapy.Compared with intravenous (IV) cyclophosphamide, MMF was as effective in achieving stable kidney function (5 studies, 523 participants: RR 1.05, 95% CI 0.94 to 1.18) and complete remission of proteinuria (6 studies, 686 participants: RR 1.16, 95% CI 0.85 to 1.58). No differences in mortality (7 studies, 710 participants: RR 1.02, 95% CI 0.52 to 1.98) or major infection (6 studies, 683 participants: RR 1.11, 95% CI 0.74 to 1.68) were observed. A significant reduction in ovarian failure (2 studies, 498 participants: RR 0.15, 95% CI 0.03 to 0.80) and alopecia (2 studies, 522 participants: RR 0.22, 95% CI 0.06 to 0.86) was observed with MMF. In maintenance therapy, the risk of renal relapse (3 studies, 371 participants: RR 1.83, 95% CI 1.24 to 2.71) was significantly higher with azathioprine compared with MMF. Multiple other interventions were compared but outcome data were relatively sparse. Overall study quality was variable. The internal validity of the design, conduct and analysis of the included RCTs was difficult to assess in some studies because of the omission of important methodological details. No study adequately reported all domains of the risk of bias assessment so that elements of internal bias may be present. AUTHORS' CONCLUSIONS: MMF is as effective as cyclophosphamide in inducing remission in lupus nephritis, but is safer with a lower risk of ovarian failure. MMF is more effective than azathioprine in maintenance therapy for preventing relapse with no increase in clinically important side effects. Adequately powered trials with long term follow-up are required to more accurately define the risks and eventual harms of specific treatment regimens.